This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.
Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, participants must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs. Participants in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, participants will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether participants with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation. Participants will be assessed before and after transplantation and will be followed ≤36 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
Cyclophosphamide 60 mg per kilogram (kg) of body weight per day intravenously (IV) on days -5 and -4 with respect to transplantation; humanized anti-CD2 monoclonal antibody (MEDI-507) 0.6 mg per kg on days -1, 0, and 1 (after test dose of 0.1 mg per kg on day -2); and cyclosporine A 5 mg per kg IV and thymic irradiation (700 cGy) on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered postoperatively, 8 to 12 mg per kg per day, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Protocol amendment that applied to participant 4 and 5: rituximab, 375 mg per square meter of body-surface area days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.
Massachusetts General Hospital
Boston, Massachusetts, United States
Graft Survival Twenty-Four Months Post Transplantation
Defined by kidney transplant survival at month 24 post transplantation with successful withdrawal of cyclosporine following transplantation, in the absence of maintenance immunosuppression.
Time frame: 24 months (2 Years) Post Transplantation
Participant Survival
During the three-year post-transplant follow-up period for enrolled participants.
Time frame: Up to thirty-six months (3 Years) Post Transplantation
Graft Survival
During the three-year post-transplant follow-up period for enrolled participants.
Time frame: Up to thirty-six months (3 Years) Post Transplantation
Change from Baseline in Renal Function Using Serum Creatinine
Changes in serum creatinine levels from baseline through post transplantation follow-up period.
Time frame: Up to thirty-six months (3 Years) Post Transplantation
Number of Episodes of Acute or Chronic Graft Versus Host Disease (GVHD)
Evaluations for suspected GVHD, including biopsies as appropriate, during routine and/or for cause assessments.
Time frame: From Week 1 through thirty-six months (3 Years) Post Transplantation
Number of Adverse Events
As defined by protocol.
Time frame: Participant enrollment through <=thirty-six months (3 Years) Post Transplantation
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NONE
Enrollment
5